Research on barium sulphate

In one study, rats inhaled barium sulfate at a concentration of 40 mg/m3, 5 days per week (5 h/day) for up to 2 months.18 The rats were killed at 2-week intervals after the beginning of the exposure period, and the barium content of the lungs, lymph nodes, jaw, and femur was determined. Lymph transport was negligible. The barium content of bone increased initially and then gradually decreased during treatment. After 2 weeks of exposure, the barium content of the lungs was high but decreased rapidly and then increased considerably over the next 4 weeks of treatment.

In another study, groups of male Wistar rats were exposed (whole-body) 5 days per week (7 h/day) to barium sulfate dust at target aerosol concentrations of 37.5 µg/m3 and 75 µg/m3.19 At each of 6 time points, 6 rats were drawn for dust burden measurements. Considering that dust deposited higher in the respiratory tract would have time to clear, animals used for lung and dust burden analyses were killed 66 hours after the end of exposure. In terms of milligram dust per gram of dry lung tissue, the burdens at the final exposure points were 24 mg/g and 17 mg/g for the high and low barium sulfate concentrations, respectively.

Following endotracheal administration of a barium sulfate containing mixture (formulated as a radiodiagnostic contrast agent for oral administration) into 220 Sprague-Dawley rats and 3 dogs, radiographic and histologic studies were performed.20 The barium sulfate containing mixture (0.25 mL), under fluoroscopic control, was injected endotracheally into rats, and a 1.75 mL/kg dose of was administered endotracheally to dogs. The 0.25 mL dose was selected based on the results of a pilot study in which all 30 rats died after intratracheal administration of 0.5 mL of this mixture. After dosing with this mixture, radiographs were obtained immediately and at 15 and 30 minutes, at 1 hour, 2 hour, 3 hours, 4 hours, 5 hours, and 6 hours, and then 3 times daily for 1 week. All of the rats and 2 dogs were radiographed for a total of 9 months. The barium sulfate containing mixture was virtually cleared from the trachea and stem bronchi in 30 minutes. It cleared more slowly from the lungs of 3 dogs when compared to these data on rats. Additional study results are included in sections on Acute Intratracheal Toxicity and Inflammatory Response.

Toxicology

Acute Toxicity

Oral

Six groups of 16 to 26 young male CBL-Wistar albino rats (ages not stated) received the following 6 total doses of barium sulfate (150% w/v suspension), respectively, by intragastric cannula: 188, 225, 263, 300, 338, and 375 g/kg.21 For each total dose, 40% was given initially, followed by 35% of the dose 3 hours later, and 25% 4 hours later. Fifty control rats were dosed with distilled water. Fifty experimental animals died from stomach rupture, and the mean LD50 was 307 ± 29 g/kg. Stomach rupture appeared to have been due, in part, to failure of the animal to pass barium sulfate along the gastrointestinal tract. In 90% of the animals, hemorrhagic areas were found in the gastric mucosa, mainly on the anterior and posterior surfaces. The adrenal glands were enlarged, the liver was small, and the stretched abdominal muscle had a watery consistency. It should be noted that, in pilot tests, barium sulfate doses ranging from 1 to 160 g/kg body weight did not cause death.

Intratracheal

Following endotracheal administration of a barium sulfate containing mixture (formulated as a radiodiagnostic contrast agent for oral administration) into 220 Sprague-Dawley rats and 3 dogs, radiographic and histologic studies were performed.20 The barium sulfate containing mixture (0.25 mL), under fluoroscopic control, was injected endotracheally into rats, and a 1.75 mL/kg dose was administered endotracheally to dogs. The 0.25 mL dose was selected based on the results of a pilot study in which all 30 rats died after intratracheal administration of 0.5 mL of the mixture. After dosing with this mixture, the protocol dictated that all of the rats and 2 dogs would have been radiographed for a total of 9 months. However, 2 of the 3 dogs dosed with the barium sulfate containing mixture (1.75 mL/kg) died during the first 24 hours; both dogs had diffuse alveolarization of the contrast agent. Diffuse, but patchy, acinar filling resulted in a slow decrease in barium aggregates from the lungs of rats and the dog over a 9-month period. New infiltrates were found in 15% of the rats on serial follow-up.